Sulphonated indole derivatives



Patented June 18, 1940 SULPHONATED INDOLE PERIVATIVES Kurt Engel, St.Louis, Ht. Rhin, France, assignoi: to J. R. Geigy S. A., Basel,Switzerland No Drawing. Original application May 12, 1937,

Serial No. 142,284. Divided and this application April 11,1938, SerialNo. 201,423. In Switzerland May 14, 1936 Claims. (Cl. 260-319) Thisapplication is a division of my application Ser. No. 142.284, filed May12, 1937.

According to this invention, new water soluble derivatives of theheterocyclic series are made 5 by treating with a sulphonating agentunder mild conditions (i. e. not substantially over C., such that no orsubstantially no colored byproducts are formed) compounds of thefollowing general structure which contain in position 1 or 2 a highmolecular aliphatic or an. alicyclic substituent with more than fivecarbon atoms, and which may be substituted in the free positions of thebenzene 20 nucleus in any desired manner, and in the remaining freepositions 1, 2 and 3 by alkyl-, aralkylor aryl-groups. The termalicyclic is to be understood to include substituents which are derivedfrom aromatic groups by hydrogenation.

As parent materials to be subjected directly or indirectly tosulphonation there come into question indoles substituted in position 1or 2 by a high molecular aliphaticor alicyclic-group having more thanfive carbon atoms. These compounds which are in part new can be obtainedby methods known for the production of indoles; thus they may easily beprepared by splitting olT water from acylated orthotoluidides by meansof sodium alcoholate at temperatures up to about 320 C. (according toMadelung, Ben,

volume 45, page 1128), or by means of sodamide at a somewhat lowertemperature (according to Verley, Bull. de la Soc. Chim. 1924 and 1925and British Specification No. 303,467). However,

other processes for preparing indole and its substitution products maybe used with equally good results.

Some methods of preparation of some parent materials for thesulphonation which have not hitherto been known will now be brieflyindicated:

One general method consists in acylating with a carboxylic acid or asuitable derivative thereof an aromatic ortho alkyl substituted aminewhich, besides the alkyl-group in ortho-position,

may contain in the benzene nucleus other substituents such asalkyl-groups and whose aminogroup may be either a primary or secondaryone containing a1ky1-, aralkylor aryl-groups, and

then subjecting the acylamide to condensation to produce the indole ringaccording to the usual methods.

According to whether the aliphatic or alicyclic radical of highmolecular weight is to be present in position 1 or 2 of the indolo ring,one of the 6" following procedures must be followed:

(1) The high molecular aliphatic or alicyclic radical is to occupyposition I in the indole.

An aliphatic or alicyclic radical containing more than five carbon atomsis introduced into 10 an ortho-alkyl-substituted primary amine. Themanner in which the 2-position is to be substituted after the indolecondensation, whether by hydrogen or by an alkyl-, an aralkyloranarylradical, determines the carboxylic acid which Iii must be used forthe acylation. For example, N-dodecylortho-toluidine may be formylatedor acetylated and the product subjected to the indole fusion; in thefirst case there is obtained l'dodecyl-indole, and in the second casel-dodec- 20 yI-Z-methyl-indole. Instead of the dodecyl radical there maybe introduced a mixed alkyl-group corresponding with lorol (that is themixture of alcohols obtainable by the catalytic reduction of coconutfatty acids), the radical of olein-al- 2'5 cohol or another unsaturatedalcohol, or the radical of a naphthene-alcohol, a terpene-alcohol, orcyclohexanol is also applicable. If instead of a formylor acetyl-radicalthere is introduced a pheny1a-cetyI-, phenoxyacetylor benzoyl-radi- 30'.cal, there will be present in 2-position after the indole ring closure abenzyl-, phenoxymethylor phenyl-group. Instead of ortho-toluidine theremay be used as parent material ortho-aminoethylbenzene, metaorparaxylidine, mesidine or other homologues of theortho-methyl-aminobenzene.

(2) The high molecular aliphatic or alicyclic radical is to occupyposition 2 in the indole.

In this case one starts from an ortho-alkylsubstituted primary orsecondary (alkyl-, aralkylor aryl-substituted) amine, acylates with afatty acid of high molecular weight such as stearic acid, palmitic acid,oleic acid, hydrogenized codliver oil fatty acid, hydrogenized soya beanfatty acid, palm-nut oil fatty acid, coconut fatty acid, naphthenicacid, resin-acid, campholic acid, fencholic acid, cyclohexane-carboxylicacid or the like, or with a suitable derivative of such an acid, andthen brings about ring closure to 50 the indole. For example,meta-xylidine may first be converted into mono-N-benzylmeta-Xylidinewhich may be then acylated with palm-nut oil fatty acid, and the productfused with sodiumethylate. There is obtained the hitherto un 55 knownl-benzyl-Z-undecyl- (mixed with lower and higher radicals)--methyl-indole.

The following is a more precise description given in illustration of themanner of preparing the indoles, the parts being by weight:

4.6 parts of sodium are dissolved in 50 parts of absolute alcohol anddistilled until half the solvent used has been evaporated, whereupon 30parts of palm-nut fatty acid ortho-toluidide are added and the wholewell mixed together. Then the mixture is slowly heated to 300 C. withefiicient stirring. Ethylalcohol first distils, and-after this has beenexpelled the reaction mixture constitutes a yellow semi-solid mass. Thesplitting oif of water occurs at a temperature range of 290-320 C. it isaccompanied .by strong foaming and is complete as soon as the melt hasbecome quiescent, the operation requiring about half an hour. After thereaction mass has cooled it is introduced into water, acidified withacetic acid, and the indole is separated or extracted by means of anorganic extracting agent, and if required is distilled in a high vacuum(boiling point l20210 C. under 0.0 mm. pressure). I

The indole mixture thus obtained is a yellowish-white crystalline masshaving a low melting ture of the indole fusion with alcoholate withoutsuffering saponification to an appreciable degree.

1 Very good yields are likewise obtained with the use of sodamide.

If in carrying out the foregoing process instead of the ortho-toluidideof palm-nut fatty acid there is used another ortho-toluidide such as rthat of an unsaturated or saturated fatty acid,

or a mixture thereof such as oleic acid, stearic acid, hydrcgenizedcodliver oil fatty acid or hydrogenized soya bean fatty acid and so on,or a N-substitution product of such toluidide,-for example N-benzylstearic acid-ortho-toluidide, N-palm-nut fatty acid-N-ethyl-ortho-toluidide, N-aceto -N-lauryl-ortho-toluidide and so on,the corresponding indoles are obtained according to the same course ofreaction. They areall yellowish-white masses and, owing to theirgenerally non-uniform nature, resemble very closely the indole mixtureabove described.

The following examples illustrate the invention, the parts being byweight unless otherwise stated, and the parts by weight and the parts byvolume being related in the same manner as the idle and the liter.

Example 1 60 parts of indole prepared from palm-nut fatty acidortho-toluidide are gradually introduced into 60 parts of sulphuric acidmonohydrate at a temperature between and 20 C. while stirring. Thesolution is cooled to 5 C. and 120 parts of oleum of 26 per centstrength are allowed to drop in slowly. After the whole has been stirredfor 4 hours at a temperature below 10 C. a sample withdrawn from themixture and neutralized proves to be completely soluble in water. Assoon as this is the case the reaction mixture is poured on to ice, thefree sulphonic acid which is precipitated is separated and neutralizedby the addition of caustic soda solution. By evaporation the sodium saltis obtained in the form of a slightly colored powder which is veryeasily soluble in water and forms solutions which foam strongly. Thealkaline earth salts of the new product are also easily soluble inwater.

A product having similar properties is obtained by causing 120 parts ofmonohydrate and 60 parts of oleum of 66 per cent strength to act on 60parts of the same indole under the conditions above indicated, or byintroducing 1 part of the indole into a mixture of 5 parts ofmonohydrate and 5 parts of chlorosulphonic acid at 10 0., stirring for14 hours, and working up as above indicated.

- Example 2 20 parts of the 2-heptadecylindole obtained by fusion withsodium-alcoho-late of the ortho-toluidide of technical stearic acid areintroduced into 30 parts of sulphuric acid monohydrate at 10 C. whilestirring, 30 parts of oleum of 26 per cent strength and afterwards 10parts of oleum of 66 per cent strength are slowly dropped in, and thewhole is stirred for 6 hours at 20 C. The reaction mixture is thenpoured on ice, the free sulphonic acid which precipitates is separated,neutralized with alkali and evaporated. There is obtained a whitepowder.

If instead of the Z-heptadecylindole the corresponding 3-phenylderivative (made from the stearoylamide of the following formulaprepared by acylating ortho-aminodiphenylmethane with the acid chlorideof technical stearic acid) is used, a similar product is finallyobtained by sulphonation.

Example 3 parts of a-heptadecenyl-indole are introduced into a mixtureof 30 parts of sulphuric acid monohydrate and 30 parts ofchlorosulphonic acid at 10 C. and the whole is stirred at thistemperature for 14 hours. As soon as a sample withdrawn from the mixtureand neutralized is soluble in water, the reaction mass is poured on toice and the precipitated sulphonic acid is separated and neutralized.There is obtained after evaporation a white powder which in aqueoussolution has good properties of capillary activity.

A similar sulphonate is obtained by dissolving 15 parts ofheptadecenyl-indole in 45 parts by volume of ether, cautiously droppingin 45 parts of ohloro-sulphonic acid, and stirring for 6 hours at -25 C.The product is worked up as above indicated.

Examp e 4 precipitated sulphonic acid is separated, neutralized, andevaporated. There is obtained a white powder having good properties ofcapillary activity.

Instead of the indoles of the above examples there may be used otherindoles such as those aaoasea disclosed above, or for example thel-lauryl-2.3- dimethyl-indo1e,the l-phenyl-2-heptadecylindole, the-stearyl or -cetyl-2-phenylindole, the indoles frombenzoyl-dodecyl-oto1uidide, from N- benayl-ortho-toluidide ofhydrogenized soyabean fatty acid, from the N-methyl-ortho-toluidide ofnaphthenic acid, campholic acid, iencholic acid, cyclohexane-carboxylicacid or their homologues derived from rn-Xylidine, mesidine. Theproducts obtained are of quite similar properties.

The new sulphonic acids and their salts obtained as described in theforegoing examples find application as capillary active agents,especially as wetting, dispersing, emulsifying, penetrating and washingagents, and in particular for emulsifying lime soaps. They are alsouseful as agents for softening, dressing and so on.

What I claim is:

1. Preparations of high capillary activity, and particularlycharacterized by their capacity for emulsifying lime-soaps, saidpreparations containing as essentially active ingredient a watersolublesalt of the indole sulphonic acid of the foilowing general formula:

wherein R represents a high molecular aliphatic radical with more than 5carbon atoms, W represents a member of the group consisting of H, alkyl,benzyl and phenyl, V represents a member of the group consisting of H,alkyl, benzyl and phenyl, and X represents a member of the groupconsisting of H and methyl, n being 1 or 2, whereby a high capacity foremulsifying limesoaps is imparted to said preparations.

2. Preparations of high capillary activity, and particularlycharacterized by their capacity for emulsifying lime-soaps, saidpreparations containing as essentially active ingredient a watersolublesalt of the indole sulphonic acid of the following general formula:

sents a member of the group consisting of H,

alkyl, benzyl and phenyl, and X represents a member of the groupconsisting of H and methyl, 11. being 1 or 2, whereby a high capacityfor emulsifying lime-soaps is imparted to said preparations.

3. Preparations of high capillary activity, and particularlycharacterized by their capacity for emulsifying 1ime-soaps, saidpreparations containing as essentially active ingredient a watersolublesalt of the indole sulphonic acid of the following general formula:

wherein a high capacity for emulsifying limesoaps is imparted to saidpreparations.

4. Preparations of high capillary activity, and particularlycharacterized by their capacity for emulsifying 1ime-soaps, saidpreparations containing as essentially active ingredient a watersolublesalt of the indole sulphonic acid of the following general formula:

wherein Y represents the radical attached to the carboxylic group in thefatty acid of palm-nut oil, whereby a high capacity for emulsifyinglimesoaps is imparted to said preparations.

5. Preparations of high capillary activity, and particularlycharacterized by their capacity for emulsifying lime-soaps, saidpreparations containing as essentially active ingredient a watersolublesalt of the indole sulphonic acid of the following general formula:

wherein Z represents the radical attached to the carboxylic group in thefatty acid of hydrogenized cod-liver oil, whereby a high capacity foremulsifying lime-soaps is imparted to said preparations.

KUR'I' ENGEL.

